Research in Western countries indicates that neuropsychological (NP) impairment is a common consequence of HIV infection and is associated with reduced everyday functioning and worse medical prognosis (early mortality). China (population 1.3 billion) is seeing an exponential growth in its HIV epidemic. Although differences in host genetics, treatment, and cofactors (e.g., other infections) may result in different neurobehavioral outcomes in China, there has been no research on neuroAIDS there. The Chinese government has placed a high priority on HIV prevention and treatment. With support of the U.S. NIH, the China CDC has initiated the China Comprehensive International Program for Research on AIDS (CIPRA), and is beginning a series of studies on two major HIV risk populations in China: injection drug users (IDUs) and former plasma donors (FPDs). Here we propose the first study of HIV related neurobehavioral disorders in China. In collaboration with colleagues at the China CDC, we will utilize the infrastructure of CIPRA and China CARES (another CDC program for HIV/AIDS) to identifiy large samples of demographically matched HIV+ and HIV- participants within the FPD and 1DU populations (4 groups, each with n=200). Over a 5-year study period, we will clarify the prevalence, nature, clinical significance, and patterns of change in HIV associated NP impairments in these groups. We will determine whether differences in NP impairment are predicted by host genetic characteristics, including specific HLA types and polymorphisms in genes encoding for chemokine receptors, chemokines, and cytokines. Effects of comorbid infection with hepatitis C virus (HCV) also will be examined, because HCV is an independent risk for NP impairment and is highly prevalent in both the IDU and FPD populations. This project extends an existing relationship between the Chinese and U.S. investigators. At an organizational level, the U.S. side will be responsible for overall study progress, training, quality assurance, and data management, while the China side will recruit, track and assess participants. The proposed research will provide detailed new information about neurocognitive and neuropsychiatric complications of HIV disease in China. This increased understanding of the clinical significance of these complications and their determinants in China should better inform clinical management of affected populations.